The objective of this project is to further investigate the enzymes responsible for the catabolism of naturally occurring galactose-terminal glycolipids, glycoproteins and oligosaccharides in human tissues. There are, at present, two distinct groups of genetic diseases of glycolipid and glycoprotein metabolism in which a deficiency of beta-galactosidase is known to be the primary enzymatic defect. One disease is called GM1 gangliosidosis because of the storage of GM1 ganglioside due to a deficiency of GM1 ganglioside beta-galactosidase. The other genetic disease caused by a deficiency of a specific beta-galactosidase is Krabbe's disease. The deficiency of galactosylceramide beta-galactosidase causes this severe leukodystrophy. A large number of variants of these diseases continue to be described and many have been seen by this investigator. In addition to these recognized diseases with primary beta-galactosidase deficiency, there are a number of other syndromes in which patients have been found to have a deficiency of beta-galactosidase secondary to some other primary enzymatic lesion. Using the large number of natural substrates available in this laboratory I propose to study human beta-galactosidases in tissues from patients with these diseases. Since a measured decrease in enzymatic activity in a given tissue can be due to a number of factors, a more detailed study in tissues showing a completely or partially deficient beta-galactosidase activity is planned. Since we have recently shown some relationship between lysosomal neuraminidase and beta-galactosidase in certain patients we would like to study this in more detail using natural and synthetic substrates.